We aim to assess the benefits and harms of low-dose hydrocortisone in patients with COVID-19 and severe hypoxia.
Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a
pandemic of coronavirus disease (COVID-19) with many patients developing severe hypoxic
respiratory failure. Many patients have died, and healthcare systems in several countries
have been or will be overwhelmed because of a surge of patients needing hospitalisation and
intensive care. There is no proven treatment for COVID-19; the care is supportive, including
respiratory and circulatory support. For other patient groups with similar critical illness
(acute respiratory disease syndrome and septic shock), corticosteroids are used because they
reduce the duration of mechanical ventilation, length of stay in the intensive care unit, and
potentially also mortality. Corticosteroids have been used in some patients with COVID-19,
but the recommendations in clinical guidelines differ; some suggest their use, others
against.
Objectives: We aim to assess the effects of low-dose intravenous hydrocortisone on the number
of days alive without life-support in adult patients with COVID-19 and severe hypoxia.
Design: Multicentre, parallel-group, centrally randomised, stratified, blinded, clinical
trial.
Population: Adult patients with documented COVID-19 receiving at least 10 L/min of oxygen
independent of delivery system OR mechanical ventilation.
Experimental intervention: Continuous IV infusion of hydrocortisone 200 mg daily will be
given for 7 days in addition to standard care.
Control intervention: Continuous IV infusion of matching placebo (0.9% saline) will be given
in addition to standard care (no corticosteroids).
Outcomes: The primary outcome is days alive without life support (i.e. mechanical
ventilation, circulatory support, or renal replacement therapy) at day 28. Secondary outcomes
are serious adverse reactions (i.e. anaphylactic reaction to hydrocortisone, new episode of
septic shock, invasive fungal infection or clinically important gastrointestinal bleeding);
days alive without life support at day 90; days alive and out of hospital at day 90;
all-cause mortality at day 28, day 90 and 1 year; and health-related quality of life at 1
year.
Sample size: A total of 1000 participants will be randomised in order to detect a 15%
relative reduction in 28-day mortality combined with a 10% reduction in time on life support
among the survivors with a power of 85%.
Drug: Hydrocortisone
Continuous infusion: 200 mg (104 ml) every 24 hours, Bolus injections: 50 mg (10 ml) every 6 hours, Total treatment duration: 7 days
Other Name: Solu-cortef
Drug: Sodium Chloride 9mg/mL
Continuous infusion: 104 ml every 24 hours, Bolus injections: 10 ml every 6 hours, Total treatment duration: 7 days
Other Name: Isotonic saline
Inclusion Criteria:
All the following criteria must be fulfilled:
- Aged 18 years or above AND
- Confirmed SARS-CoV-2 (COVID-19) requiring hospitalisation AND
- Use of one of the following:
- Invasive mechanical ventilation OR
- Non-invasive ventilation or continuous use of continuous positive airway pressure
(CPAP) for hypoxia OR
- Oxygen supplementation with an oxygen flow of at least 10 L/min independent of
delivery system
Exclusion Criteria:
We will exclude patients who fulfil any of the following criteria:
- Use of systemic corticosteroids for any other indication than COVID-19
- Invasive mechanical ventilation for more than 48 hours
- Invasive fungal infection
- Fertile woman (< 60 years of age) with positive urine human gonadotropin (hCG) or
plasma-hCG
- Known hypersensitivity to hydrocortisone
- A patient for whom the clinical team has decided not to use invasive mechanical
ventilation
- Previously randomised into the COVID STEROID trial
- Informed consent not obtainable
Aarhus University Hospital - Dept of Intensive care
Aarhus, Denmark
Rigshospitalet
Copenhagen, Denmark
Dept of Infectious diseases, Rigshospitalet
Copenhagen, Denmark
Herlev Hospital - Dept. of Intensive Care
Herlev, Denmark
North Zealand Hospital
Hillerød, Denmark
Hvidovre Hospital - Dept of Infectious diseases
Hvidovre, Denmark
Hvidovre Hospital - Dept of Intensive Care
Hvidovre, Denmark
Hvidovre Hospital - Dept of Pulmonary Medicine
Hvidovre, Denmark
Kolding Hospital
Kolding, Denmark
Køge Hospital
Køge, Denmark
Dept of Intensive Care, Odense University Hospital
Odense, Denmark
Roskilde Hospital
Roskilde, Denmark
Slagelse Hospital
Slagelse, Denmark
Viborg Hospital
Viborg, Denmark
Anders Perner, MD, PhD, Study Chair
Rigshospitalet, Denmark